Alkyl Nitrites: Novel Reagents for One-Pot Synthesis of 3,5-Disubstituted Isoxazoles from Aldoximes and Alkynes

Kishorkumar S. Kadam; Thirumanavelan Gandhi; Amol Gupte; A. K. Gangopadhyay; Rajiv Sharma

doi:10.1055/s-0035-1561464

Synthesis, Table of Contents

Synthesis 2016; 48(22): 3996-4008
DOI: 10.1055/s-0035-1561464

paper

Alkyl Nitrites: Novel Reagents for One-Pot Synthesis of 3,5-Disubstituted Isoxazoles from Aldoximes and Alkynes

Kishorkumar S. Kadam

^aDepartment of Medicinal Chemistry, Piramal Enterprises Limited, Goregaon (E), Mumbai 400063, Maharashtra, India

,

Thirumanavelan Gandhi*

^bDepartment of Chemistry, School of Advanced Sciences, VIT University, Vellore 632014, Tamil Nadu, India Email: velan.g@vit.ac.in

,

Amol Gupte

^aDepartment of Medicinal Chemistry, Piramal Enterprises Limited, Goregaon (E), Mumbai 400063, Maharashtra, India

,

A. K. Gangopadhyay

^aDepartment of Medicinal Chemistry, Piramal Enterprises Limited, Goregaon (E), Mumbai 400063, Maharashtra, India

,

Rajiv Sharma

^aDepartment of Medicinal Chemistry, Piramal Enterprises Limited, Goregaon (E), Mumbai 400063, Maharashtra, India

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Abstract

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Abstract

An efficient, one-pot approach has been described for the synthesis of 3,5-disubstituted isoxazoles from substituted aldoximes (mixture of E and Z) and alkynes, using alkyl nitrites under conventional heating conditions. The key nitrile oxide intermediates that are required for the synthesis of isoxazoles are formed by treatment of substituted aldoxime with either tert-butyl nitrite or isoamyl nitrite. The generated nitrile oxides underwent in situ [3+2] dipolar cycloaddition to the substituted alkynes to give 3,5-disubstituted isoxazoles regioselectively in high to excellent yields. The developed synthetic methodology was applied for the synthesis of a previously reported potent hDGAT1 inhibitor.

Key words

isoxazoles - nitrile oxides - aldoximes - tert-butyl nitrite - isoamyl nitrite

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References

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